Recently, I watched a ‘TED’ talk (TED is an acronym for
‘Technology, Entertainment, and Design’). The talk was given by two
neuroscientists, Steve Ramirez and Xu Liu, and took place in Boston, June 2013.
The presentation was based on research that led to several
publications that appeared in the science journals, Nature and Science. The
title of the Nature article is:
‘Optogenetic stimulation of a hippocampal engram activates fear memory recall’
and was published in early 2012, while the Science
report was entitled: ‘Creating a False Memory in the Hippocampus’ and was
published in July 2013.
All of the foregoing will be elaborated upon shortly.
However, first, I would like to create a context for the critical reflection
that will give expression to my comments concerning the research of the two
aforementioned neuroscientists.
Toward the end of the June 2013 TED presentation, Steve
Ramirez indicated that one of the purposes of their talk was to bring people up
to date on the kinds of research that were taking place in neuroscience, as
well as to acknowledge (even if only vaguely) the existence of various ethical
issues raised by their research, and, finally, to invite people to join in the
discussion with respect to their research. Steve’s co-presenter, Xu Liu, also
stipulated at one point near the end of the talk that their research was rooted
in a philosophical principle of neuron science – namely, that, ultimately, mind
is a function of physical stuff … stuff that can be “tinkered with” and a
tinkering process that is limited only by our imagination.
On the one hand, the following comments constitute my
acceptance of the aforementioned invitation from Steve Ramirez during the June
2013 presentation for people to join in the conversation concerning their research.
Consequently, part of my comments will address some of the ethical concerns
that were alluded to by Steve Ramirez during the Boston presentation, while
another aspect of my comments – perhaps the more central dimension of such
comments -- will revolve around an exploration of the philosophical principle
cited by Xu Liu that is at the heart of neuroscience and which, as indicated
earlier, seeks to reduce mental phenomena to biological, material, or physical
events.
Let’s begin by providing an outline of the experimental
model employed by Steve Ramirez and Xu Liu. Among other things, that model
involves introducing mice to a few methodological bells and whistles.
Optogenetics (a word which appeared in the title of the
aforementioned Nature article) is a
term that – as the sub-components of the word might suggest – involves
combining optical and genetic properties in certain ways. Essentially,
microbial or viral genes are engineered to become receptive or sensitive, in
some manner, to light or optical energies and, thereby, such genetic residues are
enabled to, in effect, serve as a target for light sources (e.g., lasers) that
will induce the target molecules to serve like switches that are capable of
turning certain aspects of cellular functioning on and off when the genetically
engineered concoction is injected into, say, mice and, subsequently, activated
by laser stimulation.
In their presentation, Ramirez and Liu also point out that
there is a biological marker or indicator present in cells that signifies
certain kinds of activity have taken place in those cells. Therefore, part of
the process of genetic engineering employed in the optogenetics technique is to
take a molecular component that has a sensor-like capacity that is able to
detect the presence of the aforementioned cellular indicator or marker
signifying recent cellular activity and, then, splice that sensor component to
the aforementioned molecular/genetic switch that, subsequently, can be
activated and deactivated through the application of targeted laser
energies.
In the case of the Ramirez-Liu experiments, the ‘switch’
portion of the genetically engineered component is channelrhodopsin. This is a
membrane protein that controls the flow of certain ions (for example, sodium – Na+) into the
interior of a cell. Modifying the flow of ions into a cell is possible because
channelrhodopsin is a protein whose three-dimensional conformation can be
altered when stimulated by, among other things, laser light and, in the
process, open or close the membrane channel-way with respect to ion flow,
thereby affecting the functioning of such a cell.
To sum up, the general idea employed by Ramirez and Liu in
their experiments is to identify cells that are involved in, for example,
memory formation through the manner in which those cells will leave an activity
signature or marker. This marker can be detected by the genetically engineered
sensor-switch component and, this, in turn, will transform the cell into a
target that is believed to have something to do with memory formation and which
-- when deemed appropriate by the researchers – can be activated by stimulating
the switch side (i.e., the membrane protein channelrhodopsin) of the
generically engineered virus with laser light.
For quite some time, the hippocampus (a ridge section found
along the bottom of the lateral ventricle portion of the brain – there are two
such ridge sections) has been implicated (via an array of experimental and
clinical evidence) as playing an important role of some kind with respect to
memory formation. Thus, when one scans the title of the aforementioned Nature journal article – i.e.,
‘Optogenetic stimulation of a hippocampal engram activates fear memory recall’
– and understands that the term “engram” is a way of referring to a memory
trace that has arisen through a hypothesized change (temporary or permanent) in
brain chemistry within the hippocampus, then one is being told by the Nature article title that the
Ramirez/Liu experiment is one which uses optogenetic methods (outlined
previously) to bring about the activation (or recall) of memories involving
fear.
In 2000, Eric Kandel received the Nobel Prize for research
that helped establish the nature of some of the physiological dynamics that are
associated or correlated with memory formation/storage in Aplysia -- a sea slug
whose relatively large nerve cells made it a good candidate for trying to
scientifically analyze what happens biochemically when learning or memory
formation occurs in those life forms. To make a much longer story somewhat
shorter, Kandel and other researchers discovered -- while studying the gill-withdrawal
reflex in Aplysia -- that sensitization and habituation (which are both forms of learning and,
therefore, constitute instances of memory formation) were associated with the
release of certain kinds of molecules -- [e.g., c-Amp – the so-called second
messenger of the cell, serotonin (a neurotransmitter), PKA (c-AMP dependent
kinase), and CREB (c-AMP response element
binding protein) -- that appeared
to play important roles in short-term and long-term memory formation, as well
as were implicated in the processes that converted short-term memory into
long-term memory.
The generation of the foregoing sort of cascade of
biochemical molecules also was correlated with increases in synaptic complexity
or connectivity. As a result, Kandel came to believe that changes in synaptic
connectivity were indications that learning/memory was somehow being
established through those synaptic enhancements, and, in turn, those changes in
synaptic connectivity were some kind of a function – although many of the
details were lacking with respect to the precise dynamics of that function -- of
the cascade of biochemical changes that were taking place within neurons.
Mice are more complex than Aplysia, and humans are more
complex than either mice or Aplysia. Nonetheless, ever since the work of Kandel
began back in the 1960s, a great deal more biochemical, physiological,
cellular, and neuronal evidence has been generated that is consistent with the
idea that when certain (a) biochemical changes in cellular physiology are
correlated with (b) changes in synaptic connectivity that are correlated with
(c) differences in behavioral activity over time, and when the foregoing three
elements occurred in relatively close temporal (if not spatial) juxtaposition
to one another, then the collective presence of those three elements was
interpreted to indicate that learning or memory had been generated … and, this
remains the basic idea concerning the issue of memory formation irrespective of
whether one is talking about Aplysia, mice, humans, or any other life form that
is capable of exhibiting a capacity to learn or retain memories (short-term or
long-term) with respect to on-going experience.
Naturally, the physical/material details of learning and
memory might change as one moves from species to species. Nevertheless, a
growing body of evidence lends support to the idea that learning/memory are
entirely functions of physical/material events.
The Ramirez/Liu research that was outlined in the June 2013
TED talk is a continuation of the foregoing perspective. The two investigators
took mice and surgically implanted a means of delivering laser stimulation to
the hippocampus portion of a mouse’s brain that also had been equipped with a
genetically engineered ‘sensor-switch’ which could detect recent activity in
cells that seemed to be involved in the formation of memories concerning fear
in the experimental animals.
More specifically, the researchers placed a number of
surgically altered, and genetically engineered mice into a chamber where an
electrical shock was applied to the feet of the animals. As a result of this
experience, certain cells in the hippocampus portions of the mice brains became
active, and this activity left a biochemical footprint that was detected by the
genetically engineered sensor-switch which had been injected into the mice
through a viral host and, as a result, served as target candidates for
subsequent laser stimulation.
The fact specific cells became active during the shocking
process was interpreted by the researchers to signify that a memory had been
formed. However, a number of questions can be raised concerning that kind of
interpretation.
To begin with, what does it mean to say that a cell has left
a marker indicating that the cell has been active recent? Active doing what?
The presumption of Ramirez and Liu is that the cellular
activity gives expression to processes that are involved in learning or memory
formation. However, one could ask in relation to such activity: Involved how?
How does a neuronal cell’s activity generate learning or
memory formation? Where, exactly, is the memory amidst such cell activity?
Is learning/memory in the cells that have been activated? If
so, what is the form of the dynamic structure or process that is said to ‘hold’
the memory in the cells – whether considered either individually or
collectively? Or, is the memory of fear to be found in the synaptic changes
that follow from the changes in cell chemistry. Or, is it some combination of
the foregoing two possibilities.
According to Ramirez and Liu, the process works as follows.
First, the three-dimensional conformation of channelrhodopsin is induced to
change. As a result, certain ions
begin flowing into the interior of the cell.
In turn, the ion influx leads to a cascade of metabolic
processes involving, among other things, c-AMP, serotonin, CREB, PKA, and other
bio-molecules. Where is the memory or learning in all of this, and how did this
cascade of cellular denizens come to signify or be interpreted to mean “fear”?
Kandel and others believed that the foregoing cascade of
events was functionally related to changes in synaptic connectivity and that it
was this transformation in synaptic connectivity and complexity which signified
that learning had occurred or a memory had been formed. So, does the memory
reside in the synaptic connections, and, if so, how is the memory instantiated
in those connections, and if the memory is held through those synaptic
connections, what determines the holding pattern and what ‘reads’ that pattern
to understand that it is a memory which holds one kind of learning rather
another?
What is the relationship between, on the one hand, cells
(the sort of cells in which Ramirez and Liu are interested and for which they
have genetically engineered their sensor-switch mechanism) that are active
during memory formation and, on the other hand, changing synaptic connectivity
(which people such as Kandel believed was central to learning and memory
formation)? If memory is in the cells – as Ramirez and Liu seem to believe –
then what is the significance of the changes in synaptic connectivity and how
does what transpires in the cell shape, color, and orient those synaptic
changes?
Alternatively, one might ask what determines which cells
will be initially activated to become part of the fear learning or fear memory
process? Or, what determines which biochemical, electrical, and physiological
changes will take place within cells that will permit an organism to
differentiate learning/memory experiences over time. After all, if the same
cellular components (e.g., c-AMP, serotonin, PKA, CREB, etc.) are thought to be
at the heart of memory formation, then how are those components put together in
distinct packages that would enable an organism to differentiate among
memories? Or, what determines the pattern of synaptic connectivity that will
take place and which can be said to hold – allegedly – this or that form of
memory/learning, and what is it about the structural or dynamical character of
enhanced synaptic connectivity that gives expression to memory?
One might also critically reflect on the nature of the
differences between the original existential circumstances that led to the –
alleged – formation of a fear memory, and the quality of that memory relative
to the actual event. People who suffer from PTSD have vivid, intense,
flashbacks, and, consequently, there seems to be a dimension of intensity
associated with such flashback memories that is comparable to the original
circumstances out of which the memories arose.
However, memories are not always as vivid and intense as the
original circumstances from which they were derived or on which they are based.
So, the fact that a given memory in a mouse is activated doesn’t necessarily
explain – in and of itself – why such a memory should necessarily lead to the
response of freezing, and, therefore, one is left with the possibility that
something might be going on in the experiment other than what Ramirez and Liu
are hypothesizing to be the case.
Mice appear to have some degree of awareness or
consciousness. How do cellular and synaptic changes generate phenomenology or
how does phenomenal experience arise out of those changes?
When a mouse receives a shock to its feet, does the mouse
experience fear or does it experience pain? Or, is the mouse experiencing
stress?
There is a behavioral response in mice known as “freezing”.
This consists in a set of behavioral dispositions in which the mouse remains
very still and, possibly, vigilant when immersed in a given existential
situation that is considered threatening in some way.
Once a mouse has been shocked and, then, subsequently,
exhibits, freezing, this doesn’t necessarily mean that the mouse is
experiencing fear or remembering fear while in the condition of freezing
(although this might be the case). Instead, the mouse might be exhibiting a
form of coping strategy (which could be instinctual rather than learned) that
is intended to either help avoid subsequent shocks or deal with the pain of
having been shocked, and if so, perhaps the primary phenomenological component
under such circumstances is merely heightened vigilance with an inclination in
the mouse toward escaping or avoidance when possible.
Alternatively, freezing in mice might represent a state of
shock. Possibly, a mouse that is exhibiting freezing behavior might not either
be in pain or in a state of fear, but, rather, is just stunned and
directionless with respect to how to proceed or what to do next … somewhat like
a prize fighter who has been rocked by a punch and is merely trying to stay on
his or her feet but with very little focused awareness with respect to just
what is going on around him or her.
A variation on the foregoing possibility is that ‘freezing’
in mice might be a response to stress rather than an expression of fear. Pulled
in different direction by various internal and external forces, a mouse might
freeze up, and, consequently, the associated phenomenological state is one of
stress rather than fear.
The fact of the matter is that we don’t know what is going
on in the phenomenology of a mouse during the state of freezing. Is the mouse
afraid, in pain, in shock, stressed, uncertain, vigilant, wanting to get away, remembering
a previous, similar problematic experience, or is the mouse experiencing some
combination of all of the foregoing possibilities? We don’t know.
Freezing is a behavioral disposition that is exhibited by
mice during certain circumstances. Freezing in mice is a coping strategy and/or
an instinctual behavioral response.
Learning or memory formation might play some sort of
modulating role with respect to how that behavioral response manifests itself
within different circumstances. Nevertheless, we don’t necessarily understand
what is triggering the behavioral response of freezing or what the precise
properties and dynamics of the triggering event are.
Is the freezing response being triggered by a memory? If so,
how does the memory lead to the initiation of the behavior?
Moreover, mice have a more expansive repertoire of behavior
than just freezing. Sometimes they fight and sometimes they take flight?
What if the freezing is an indication that the mouse is
uncertain about whether to pursue fighting or fleeing? What if the freezing
indicates indecision rather than fear, stress, pain, or shock?
Perhaps, freezing means different things to a mouse in
different circumstances. On some occasions, it might be an expression of fear,
but on other occasions it might indicate stress, indecision, or a vigilant wait
for the sort of information that might push the mouse toward fighting or
fleeing.
We don’t know what, if any, phenomenology is associated with
that behavioral response. We don’t know what, if anything, the cellular and
synaptic changes that have been described by neuroscientists since the time of
Kandel have to do with the generation of that phenomenology.
There is no neuroscientist on the face of the Earth who has
yet been able to demonstrate how one goes from cellular changes in neurons to
enhanced synaptic connectivity, and, then, is capable of proceeding on to demonstrate
how the phenomenology of memories of a particular character and quality arise
from those cellular and synaptic changes. All scientists have established so
far is that there is a correlation between certain kinds of biological events
and the appearance of the sorts of behavior that seem to suggest that learning
has taken place or a memory has been formed, but, unfortunately, some
scientists have jumped to unwarranted conclusions concerning the connection between
biological activity and the phenomenology of experience.
Consider the following idea. One can probe the electronic
intricacies of a television set all one likes – even down to the quantum level.
However, such analysis will do nothing to tell one where the content and
structure of the picture comes from that is made manifest through the
television set.
As is the case with television sets, so too, biology, cell
physiology, and synaptic connectivity might play a necessary supporting role
with respect to the phenomenology of experience. Nonetheless, biology alone
might not be sufficient to account for the character of the content that is
given expression through the phenomenology of experience.
A television set plays a necessary supporting role with
respect to being able to generate a picture on its screen but that same
electronic device cannot account for why the picture has the content,
structure, and quality it does. To account for the latter phenomenon, one needs
to talk about television stations, writers, authors, directors, actors,
producers, and viewers … all of which exist beyond the horizons of the
television set, just as a proper explanation for memory or learning might exist
beyond the horizons of purely biological considerations – at least as those
considerations are currently understood.
Let us return to the Ramirez/Liu experiment. Under normal
circumstances, when a mouse is placed in an experimental box, the animal
exhibits exploratory behavior … sniffing and scurrying its way around the
interior of the apparatus.
If the feet of the mouse are shocked during the exploratory
process, the mouse, subsequently, might begin to display freezing behavior.
According to Ramirez and Liu, the mouse has formed a memory of fear, and this
state of fear leads to the behavioral response of freezing.
However, as indicated earlier, we really can’t be certain of
what is taking place within the phenomenology of the mouse. The mouse might be
experiencing fear, but, as well, the mouse also might be experiencing a phenomenology
of vigilance, avoidance, stress, shock, and/or pain along side of the fear or
instead of such fear.
If shocked for a sufficiently long period of time with no
possibility of escape, the mice also might come to exhibit the same sort of
‘learned helplessness’ that Martin Seligman discovered occurred with respect to
dogs when they were exposed to inescapable shocks. Under such circumstances,
the freezing might be a sign of learned helplessness rather than a state of
fear per se.
Learned helplessness is a more complex phenomenological
state than fear since it consists of the integration of a set of experiences
rather than being a function of just one experience. Yet, the differences in phenomenological state between fear
and learned helplessness both might end up being manifested through the same
freezing behavior.
Ramirez and Liu arrange for the genetically engineered
channelrhodopsin switch to be activated through the application of a pulse of
laser light. This sets in motion a series of cellular biochemical and
physiological changes, and, then, freezing behavior is exhibited.
What actually has happened? Has a memory been activated and,
then, that memory causes freezing behavior to appear?
Even if it is the case that a certain memory has, somehow,
been activated through the activation of the channelrhodopsin switch, can one
be sure that the biological situation is not unlike a television set which has
been switched on, and, yet, the picture which appears is not – strictly
speaking – caused by the turning on the television set. Rather, the turning on
of the television set is little more than a necessary precursor for gaining
access to a picture (memory) that is generated through an entirely different
process occurring outside of the electronic circuits of the television set.
Does the laser-activation of those cells that were active
during the process of memory formation (when the unfortunate mice were shocked)
represent the recall of a specific kind of memory? Or, does the
laser-activation of such cells merely set in motion a sort of ‘learned reflex
arc’ or ‘behavioral circuit’ that results in freezing behavior without the
middleman of memory mediating between laser pulse and the condition of
freezing?
We see the pulse of laser light being applied. We see the
freezing behavior.
Ramirez and Liu hypothesize that the two events are bridged
by the experience of a memory of a specific kind that has been activated by a
pulse of laser light. However, they are unable to provide a plausible
explanation that can take one step-by-step from the point of initiation (laser
stimulation) to the terminal point of behavior and show that what was
transpiring involves a memory of a certain kind and the existence of that
specific memory caused the observed behavior.
The fact of the matter is that Ramirez and Liu can’t even be
certain what kind of memory was laid down during the process of shocking. They
claim the memory is one of fear, but they can’t prove this because they can’t
eliminate the possibilities that the memory that formed might have contained
elements of stress, pain, shock, and indecision, and not just fear.
Or, perhaps, fear was not part of the original memory
phenomenology at all. After all, one might argue that the original memory was
one of pain, not necessarily fear, and, therefore, fear is a secondary
emotional response to the perception of pain.
Did the laser-activation of cellular activity give
expression to a memory of pain rather than fear? If so, then the title of their
Nature article is, at best, misleading,
and at worse, it is incorrect.
Moreover, if the original memory was of pain, then, how does
the secondary event of fear come into the picture? How does laser-activation of
a pain memory bring about an emotional response of fear that, in turn, brings about
freezing behavior? Is the experience of fear a second memory different from the
memory of pain, and isn’t it possible that pain might be associated with other secondary
phenomenological states (e.g., stress, flight, fight, vigilance, and shock)
that could just as easily lead to a freezing response?
Ramirez and Liu can see into the structure of their
experimental situation only a little farther than their laser-activation of the
channelrhodopsin. They know that such activation will set in motion a cascade
of biochemical and physiological changes (the sort of changes explored by Eric
Kandel and others), and they know that those changes will be followed by
changes in synaptic connectivity.
However, they really don’t understand what any of this
actually means other than the fact that, collectively speaking, it is all
correlated with memory formation. The rest is all conjecture and speculation.
During the Boston presentation, Ramirez spoke of giving the
mouse “a very mild foot shock”. One wonders why a mouse would develop a fear
memory if the shock were so “very mild”? Clearly, euphemistical language is
being used to mask a process that is more painful than the phrase “very mild”
might suggest.
Nothing was said during the Ramirez/Liu presentation (by
either the researchers or the audience) with respect to the ethical issues
entailed by treating animals in the way they were treated during the
experiments that were the focus of the TED presentation. This was true both
with respect to surgically altering the heads of the mice to accommodate a
laser delivery system as well as in relation to shocking the mice, and, so, the
ethical issues to which the researchers were vaguely alluding during their
presentation involved something else other than the treatment of life forms
within the lab.
When I was an undergraduate, I participated in an experiment
involving the delivery of shocks, and the nature of the experiment was such
that I was the one who delivered the shocks to myself. For me, there was a clear phenomenological
difference between those shocks that were very mild and those shocks that were
painful and might lead to a sense of fear, stress, shock, and/or anxiety if
they were to continue.
In a rather startling expression of egocentricity, the
researchers appeared to be talking in terms of what they considered to be a
very mild foot shock, with nary a spoken worry about what the mouse might have
thought or felt about the whole affair. Nonetheless, the word that appears in
the title of their Nature article is “fear” – the article title didn’t say
anything about ‘a very mild shock memory recall ’, but, rather, used the phrase
“fear memory recall”.
Presumably, there is a difference in learning and memory
formation with respect to different kinds of stimuli. The phenomenology of the
experience involving “a very mild foot shock” is likely to be different than
the phenomenology of an experience involving a shock deemed to be capable of
generating a memory formation of fear.
So, even if one were to accept at face value everything that
the two researchers said with respect to the nature of their experiment and the
way in which it supposedly tapped into memory formation, there is a question
that remains. Was the memory that was established in the mice one of fear, or
of a very mild shock, or of something much more complex?
What exactly was in that memory? The researchers claim that
the memory was one of fear, but even if this were true, that fear occurred in a
context.
In other words, the shocks took place in an experimental
apparatus within a laboratory. The air had a smell. The box had a smell. There
were sounds. The box had a feel to it. There were visual qualities present
within the box. The surgically implanted mechanism had a ‘feel’ to it.
The foregoing context served as horizon to the experience of
the shock. The memory was not just a matter of the alleged fear but, as well,
the memory involved certain aspects of the context surrounding the shock.
How are the foregoing sorts of contextual factors coded for
with respect to either the cascade of cellular activities that occur in
connection to memory formation or with respect to the subsequent alterations in
synaptic connectivity? This is not an insignificant issue because, as we shall
soon discover, it plays an important role within the Ramirez/Liu experiment.
More specifically, according to the two researchers, if one
places a mouse that has been shocked in one laboratory box into another,
different box, then the mouse will start out by behaving as any mouse tends to
do when introduced into a new environment. In other words, the male or female
mouse will begin to explore the box and does not exhibit freezing behavior. All
of this changes when a laser is used to activate the channelrhodopsin membrane
molecule in those cells that have been identified by the injected genetically
engineered sensor-switch as having been active during the process of memory
formation in the shock phase of the experiment.
When the laser is used to re-invoke the ‘fear memory’ by
changing the three-dimensional conformation of the channelrhodopsin that leads
to the flow of ions into the cell and sets in motion a cascade of biochemical and
physiological events associated with memory, mice that previously have been
shocked will exhibit the freezing response. According to Ramirez and Liu, the
mouse is being induced to remember the original experience of fear and responds
accordingly – that is, the mouse freezes.
In their Boston presentation, Ramirez and Liu discuss how
they have added a few wrinkles to their experimental design. For example, they
talk about, first, taking surgically altered and genetically engineered mice
and placing them in a blue box, and, then, identifying the cells that are
active in the presence of such ‘blueness’.
Before proceeding on with an account of the experiment, it
seems to be appropriate to pause briefly and ask a question. How does one know
that the cellular activity being identified by the researchers through their
genetically engineered sensor-switch has to do specifically with blueness
rather than some other feature of the experimental set-up, and, moreover, even
if one were to accept the idea that the cellular activity has something to do
with retaining a memory of blueness, once again, one can raise the question of
what, precisely, such activity has to do with memory formation?
How –
specifically -- is ‘blueness’ being encoded via the cascade of cellular events
that are occurring during the learning of, or memory formation concerning,
blueness, and how does this particular package or set of cellular events
translate into unique changes in synaptic connectivity concerning the issue of
blueness? Moreover, how is this aspect of learned or remembered blueness
separated from, or integrated into, the context of other sensory experiences
that form the context surrounding the experience of blueness?
In addition, one might ask why certain cells are selected
for the memory of blueness, while other cells busy themselves with the memory
of different sorts of sensory modalities. Or, one also might wonder how the
work of an array of active cells concerning different facets of a experiential
context become integrated to generate a unified phenomenological experience
that can be understood in one way rather than another by a given life form? [By
way of a personal aside, for reasons obvious and not so obvious, all of this
talk about red and blue boxes led to my thinking about the contents of the
so-called ‘Blue’ and ‘Brown’ books of Ludwig Wittgenstein which I
read as an undergraduate].
Now, let’s return to the Ramirez/Liu experiments. In the
first stage of one of their experiments involving a blue box, nothing happens
to the mice. They just get to explore the box.
In the next phase of the experiment, the mice are placed in
a red box. While in the red box, a laser pulse activates the cells that were
identified as being active during the blue-box experience, and, as well, the
mice are given – I am quite certain – a very mild foot shock to generate a
‘fear’ memory that is now associated with a re-invoked or recalled memory of
the blue box.
In the final state of this experiment, the mice are placed
back in the blue box where they have never been shocked. Yet, as soon as the
mice are placed in the blue box, they exhibit freezing behavior.
Ramirez and Liu maintain they have created a false memory in
such mice. I have a little difficulty understanding how the two researchers
arrived at their conclusion.
But, let’s deal with first things first. Ramirez and Liu
speak about an association being established between two things. On the one
hand, there is the re-invoked memory of blueness, and, on the other hand, there
is the shock that is given in the red box while the memory of blueness is
re-invoked.
There is no false memory that is being created in the
foregoing scenario. The association being established is not a false memory,
but, rather, it constitutes the blending together of two facets of the red box
context – namely, a shock and the experience of blueness.
This is an example of classical conditioning. One takes a
stimulus – blueness – and pairs it with another stimulus – shock – to generate
a behavioral response – freezing -- that can be initiated by the presence of
blueness alone even without a shock being administered, and even though blueness
had never before been experienced as being ‘fear-stress-shock-pain-avoidance’
related.
The mice are not misremembering the original experience of
blueness. They have been taught something new during the time spent in the red
box … that is, they have been taught how the presence of blue can be
threatening, and when the mice are placed back into the environment of the blue
box, they are induced to enter into the condition of freezing because of what
they learned in the red box.
Beyond the foregoing considerations, there is the problem of
understanding the dynamics of association. How does the memory of association
work?
Everyone talks in terms of the capacity of various life
forms to associate different aspects of experience whether through temporal and
spatial juxtaposition. We all know that such a phenomenon is real, and we all
note evidence of its presence through a wide variety of circumstances involving
human beings and other life forms.
Nevertheless, no one really knows how it works. No one understands
the dynamics of association. We only acknowledge the result of that dynamic.
How does the memory of blueness and the memory of being
shocked – very mildly -- enter into a new, modified understanding within the
context of a the red experimental box that is capable of generating, say, the
freezing response in mice? How does what happens in those cells which are
active during the formation of a memory of blueness become intertwined with
what happens in those cells that are active during the experience of being
shocked?
One might suppose that there are many neuronal cells that
are active during any given experience. Why is blueness singled out as the
feature that is to be mixed with the sensory experience of being shocked?
Phenomena such as generalization do occur (as is evidenced
by my previously noted aside concerning Wittgenstein’s Blue and Brown books in
which some sort of generalization took place in relation to the blue and red boxes of the Ramirez and Liu
experiments). Various life forms do transfer certain aspects of learning or
memory developed in one context to a broader array of contexts that are in
some, as of yet, mysterious way acknowledged or arbitrarily designated as being
similar to the original context of learning.
Unfortunately, we don’t really know or understand much about
how any of this actually works. We see all kinds of correlations, but we have
little idea of how everything fits together and generates or causes this or
that memory or this or that understanding or this or that belief or this or
that instance of learning, and this remains true even with respect to the
simplest of cases involving learning and memory formation such as in instances
of: habituation, sensitization, association, conditioning, or generalization.
The experiments conducted by Ramirez and Liu really haven’t
gotten us any closer to understanding the specific dynamics of either memory,
learning, or how the phenomenology surrounding such experience arises. More specifically, their work hasn’t
helped to show us how to bridge the gap between, on the one hand, changes in
the internal biochemistry or physiology of neurons and synaptic connectivity,
and, on the other hand, the actual, causal dynamics of learning and memory as a
function of the former material changes, nor are we able to explain in a
plausible, consistent, rigorous, coherent fashion how changes in neurons and
synaptic connectivity become manifested in phenomenological, conscious states
that are characterized by differential qualities that are integrated into a
unitary sense of experience concerning reality – and quite independently of
whether such unified phenomenology actually accurately reflects the nature of
some aspect of that reality.
Ramirez and Liu only have provided us with some more
correlations. These might be interesting correlations, but, in the end, that is
all they are.
The methodological techniques that have been devised and are
used to demonstrate the existence of certain correlations are quite innovative.
Nonetheless, the bottom line on all this ingenious innovativeness is that
nothing which they have said in their TED talk or in corresponding articles
gets us any closer to understanding how the dynamics of memory and learning
work, and, certainly nothing which they have said demonstrates the truth of the
underlying philosophical premise that mind can be shown to be a function of
purely material events –- events that can be tinkered with.
This leads to a further issue. Toward the end of the Boston
TED talk, Xu Liu talked about how we are living in very exciting times in which
science is not tied down by any arbitrary limits with respect to progressing in
our understanding and knowledge concerning such phenomena as memory and
learning. In effect, science is bound only by our imaginations.
Unfortunately, the imaginations of some people are more
problematic and disturbing than are the imaginations of other people. The
Defense Department subsidizes a great deal of the scientific work that is
taking place in academia and in the corporate sector (both are integral parts
in the military-industrial complex), and, as luck would have it, the people who
are in control of that Department imagine all kinds of things with respect to
the arbitrary uses to which scientific research can be put -- uses that end up
killing, maiming, hurting, and enslaving people … both foreign and domestic.
Although the research of Ramirez and Liu has not
demonstrated the generation of false memory, that research has revealed some
possible techniques for interfering with the minds of life forms. How long will
it be before the research of people like Ramirez and Liu is weaponized and
applied against whomever the people in power deem to be appropriate.
We don’t live just in the exciting times about which Liu
enthuses. We also live in very perilous and authoritarian times … times in
which all too many governments are quite prepared to do whatever is necessary
to stay in power, control resources, and induce citizens to serve that power.
Ramirez and Liu are very naïve if they believe their research is only about scientific
progress, and they also are in denial if they suppose that they do not have a
moral responsibility with respect to the possible applications of their work.
Speaking vaguely about the ethical implications and ramifications
of their research work after the fact has got things backward. They should have
been concerned about those implications before they did their research, and, in
fact, those ethical deliberations should have impacted their decision about
whether, or not, such research should have been undertaken at all.
The Ramirez/Liu research dredged up memories within me of
Michael Crichton’s book: ‘The Terminal Man’. Like the scientists in the
book, neuroscientists today are full of all kinds of swagger and arrogance with
respect to their technical proficiency and ingeniousness, and, unfortunately,
like the scientists in Crichton’s book, they are ignorant of their own
ignorance concerning the many lacunae between what they believe they know and
the actual nature of reality.
The scientists in Crichton’s book believed they knew what
they were doing. They didn’t, and their ignorance cost the lives of quite a few
people.
The neuroscientists of today believe they know what they are
doing. They don’t, and the problematic ramifications of that ignorance might
only manifest itself after difficulties or tragedies of one kind or another
arise.
The many physicists who worked on the Manhattan project
believed they knew what they were doing. Few of them grappled with the horrors
of Hiroshima or Nagasaki before the fact except, perhaps, Oppenheimer who
quoted from the Bhagavad-Gita after witnessing the Trinity test: “Now I am
become Death, the destroyer of worlds”.
There were many physicists and other scientists who worked
to bring nuclear technology into the real world. Those scientists seem
unconcerned – before the fact -- about the possibilities of Three Mile Island,
Chernobyl, and Fukushima becoming future realities, or about the problems surrounding
the disposal of nuclear wastes, or the use of depleted uranium as weapons of
mass destruction.
T.S. Eliot said: “Where is
the wisdom we have lost in knowledge? Where is the knowledge we have lost in
information? Ramirez and Liu, along with a great many other researchers have a
lot of information but do not seem to have much in the way of either knowledge,
or more importantly, wisdom.
More specifically, I worry about people – such as Ramirez
and Liu – who believe they understand what is going on with their experiments
when this is just not the case and which, I believe, the foregoing discussion
has helped to demonstrate. We already have seen the terrible consequences that
have ensued, and are continuing to ensue, from the self-serving arrogance of
the pharmaceutical industry with respect to its psychoactive concoctions that
are based on a form of technical wizardry that is entirely devoid of any real
understanding concerning the human mind, but, is, instead, rooted in a bevy of
correlations which are not understood, and, yet, recklessly, the pharmaceutical
industry and the FDA are permitting – if not rushing -- all manner of drugs
into the market that are generated through spurious science in their attempt to
create life-time dependencies (rather than cures) with respect to this or that
psychoactive drug.
As people such as Joanna Moncrieff (The Myth of the
Chemical Cure) a psychiatrist from England, and Peter Breggin (Medication
Madness), a psychiatrist from the United States, have pointed out,
neuroscientists have very little understanding of how psychoactive drugs
metabolize within human beings or how the actual dynamics of their ‘effects’
transpire. The existence of side effects lends support to the foregoing claim.
I know of no pharmacological study that begins with a set of
predictions concerning the precise array of side effects that will arise in
conjunction with the use of a given psychoactive agent. They do not make such
predictions because they don’t actually know what happens in people when such
drugs are taken.
For instance, there are many scientists and clinicians who
speak in terms of the idea of “chemical imbalances’ being the cause of various
emotional and mental problems, and this mythology is present in the marketing
campaigns for an array of pharmaceutical products being advertised on
television. Let’s consider the case of SSRI – that is, selective serotonin
re-uptake inhibitors.
I don’t know of any neuroscientist who has provided a
convincing argument about how the absence of serotonin causes depression or how
the absence of serotonin leads to the sorts of symptoms that are associated
with clinical depression. Moreover, there is also the rather embarrassing fact
that when independent, double blind studies are done concerning the efficacy of
SSRIs, those drugs have been shown to be no more effective than placebos.
To whatever extent pharmaceutical agents ‘work’, they do so
by masking problems, not curing them, and in the process, those psychoactive
agents dull, if not destroy, many facets of emotional life, awareness, and
human sensitivity. Unfortunately, the losing of one’s humanity is confused with
the alleged effectiveness of a given drug with respect to a change in a user’s
symptom profile.
Scientific methodologies are one thing. Conjecturing about
the significance and meaning of the experimental results that are run through
those methodologies is quite another issue altogether.
Ramirez and Liu do not have a theory of memory or learning.
They have a series of conjectures based on a problematic understanding concerning,
and interpretation of, the correlational dimensions of their own experiments
and the experiments of other individuals working in the area of mind/brain
research.
The issue before us is the following one. Are
neuroscientists on the right track with respect to their attempt to reduce
mental phenomena to some set of physical dynamics and, therefore, the work of
researchers like Ramirez and Liu represents important steps along an inevitable
path that will take us to the promised land of full understanding and a
complete explanatory account of how mental phenomena are all functions of
underlying biological events? Or, alternatively, are neuroscientists on an
asymptote path that generates ever more tantalizing correlations which will
never permit them to reach the promised land of complete explanations and,
instead, will permit them to only provide accounts of mental phenomena that
will always be inherently flawed because there are more realities in heaven and Earth, Horatio, than can be dreamt of in their philosophies.
I believe the foregoing critical analysis of the Ramirez and
Liu experiments leads to more than a few questions about just what it is that
neuroscientists know with respect to the nature of mental phenomena such as
memory formation. Maybe, eventually,
they will reach the promised land of ‘Full Explanations’, but right now they
are stuck in the entangled underbrush that populates the land of descriptions that
are based on proliferating correlations, and they don’t seem to have much, if
any, real understanding, knowledge, or wisdom concerning the actual nature of
the mind.
